Today, cancer is viewed as a genetic disease and many genetic mechanisms of oncogenesis are known. The progression from normal tissue to invasive cancer is thought to occur over a timescale of 5-20 years. This transformation is driven by both inherited genetic factors and somatic genetic alterations and mutations, and it results in uncontrolled cell growth and, in many cases, death. In this article, we review the main types of genomic and genetic alterations involved in cancer, namely copy-number changes, genomic rearrangements, somatic mutations, polymorphisms, and epigenomic alterations in cancer. We then discuss the transcriptomic consequences of these alterations in tumor cells. The use of "next-generation" sequencing methods in cancer research is described in the relevant sections. Finally, we discuss different approaches for candidate prioritization and integration and analysis of these complex data.